SEQUENCE OF A HUMAN BRAIN ADENYLYL CYCLASE PARTIAL CDNA - EVIDENCE FOR A CONSENSUS CYCLASE SPECIFIC DOMAIN

A cDNA coding for a human brain adenylyl cyclase was isolated and sequenced. The deduced partial 675 amino-acid sequence was compared with those of other known adenylyl and guanylyl cyclases. Comparison of this predicted amino-acid sequence with that of bovine brain (type I) and rat olfactory (type III) adenylyl cyclase indicated a significant homology with the corboxyl-terminal halves of both enzymes. The homology between the human adenylyl cyclase and the other two mammalian adenylyl cyclase also appears at the topographic level. Indeed, the human enzyme includes an extremely hydrophobic region containing six potential membrane-spanning segments followed by a large hydrophilic domain. At the beginning of the hydrophilic domain, these is a 250 amino-acid region which shows not only a striking homology with the bovine and rat adenylyl cyclase (86% of similarity and 57% of identity), but also a significant homology with non-mammalian adenylyl cyclase and guanylyl cyclases. We found that this 250 amino-acid domain contains a sequence of about 165 amino-acid which is highly conserved in most of the known nucleotide cyclases suggesting that it includes residues that are critical for the function of the enzymes. © 1991.